A quantitative analysis of microcirculation during healing of split-thickness skin grafts in standardized full-thickness wounds.

BACKGROUND: Full-thickness skin defects often are managed with split-thickness skin grafting. The wound healing process, including formation of new vessels during the healing of skin grafts, is complex. OBJECTIVE: To evaluate the microcirculatory changes in the treated tissue after skin grafting to analyze perfusion dynamics during the wound healing process. MATERIALS AND METHODS: Fourteen full-thickness skin defects were created on the back of 14 adult male Lewis rats. All wounds were treated with autologous split-thickness skin grafts. The perfusion dynamics were assessed for 84 days with an O2C device that combines a laser light to determine blood flow and white light to determine postcapillary SO2 and the rHb. RESULTS: Blood flow increased for 50 days after grafting. SO2 decreased in superficial skin layers (depth of 2 mm) and increased in deep skin layers (depth of 8 mm) during the entire observation period. The rHb increased until day 10 in superficial layers and until day 20 in deep tissue layers. CONCLUSION: The microcirculatory changes reflect the different phases of wound healing. Long after the skin transplants were macroscopically healed, alterations in microcirculation were still detected. These alterations were caused by the long-lasting changes in tissue metabolism due to the formation, conversion, and degradation of the dermal matrix and vessels during wound healing and scar formation.

[Rhizarthrosis: Resection Arthroplasty versus Resection Suspension Arthroplasty - Still the Gold Standard?] / Rhizarthrose: Resektionsarthroplastik versus Resektionssuspensionsarthroplastik ­ immer noch der Goldstandard?

Rhizarthrosis is one of the most common arthritic changes in the hand, which has led to the development of a large number of surgical methods in recent years. In addition to the traditional resection arthroplasty with tendon suspension or interposition, if needed, thumb saddle joint prostheses are being used more and more frequently. However, these are not an option for all patients such as those with severe osteoporosis, severe nickel allergy, insufficient height of the trapezium or STT osteoarthritis. This study examined whether the traditional surgical methods continue to have their "right to exist" or whether they will be replaced by prostheses. In a retrospective study with prospective data collection, 48 hands of 45 patients diagnosed with rhizarthrosis in stages II and III according to Eaton and Littler were clinically examined 2.5 years after resection arthroplasty/resection-suspension-interposition arthroplasty using flexor carpi radialis (FCR) or abductor pollicis longus (APL) tendon strips in the years 2015-2018. The postoperative outcome was assessed using mobility, grip strength, two-point discrimination, postoperative satisfaction with regard to pain and resilience, as well as the DASH and MHQ questionnaires. There were no significant differences in surgery duration, inability to work, time to full weight-bearing, pain, satisfaction, grip strength and mobility. Regardless of the surgical method used, patients achieved an almost free range of motion in the thumb and wrist as well as age-appropriate hand strength. Pain at rest was rare; 48% were pain-free during exercise. The DASH questionnaire scored 20.2, 13.9 and 22.1 points and the MHQ scored 76.3, 79.3 and 79.4 points. Hence, the traditional surgical techniques showed good postoperative results with high patient satisfaction. "Newer procedures" such as endoprosthesis offer promising results in terms of faster regeneration times. However, this is offset by a longer surgery time and higher material costs, which means that resection arthroplasty represents a long-established procedure with a low potential for complications and a lower revision rate and should continue to be used, especially if there are relative contraindications to an endoprosthesis.

Increased Levels of BAMBI Inhibit Canonical TGF-ß Signaling in Chronic Wound Tissues.

Chronic wounds affect more than 2% of the population worldwide, with a significant burden on affected individuals, healthcare systems, and societies. A key regulator of the entire wound healing cascade is transforming growth factor beta (TGF-ß), which regulates not only inflammation and extracellular matrix formation but also revascularization. This present work aimed at characterizing wound tissues obtained from acute and chronic wounds regarding angiogenesis, inflammation, as well as ECM formation and degradation, to identify common disturbances in the healing process. Serum and wound tissues from 38 patients (N = 20 acute and N = 18 chronic wounds) were analyzed. The patients' sera suggested a shift from VEGF/VEGFR to ANGPT/TIE2 signaling in the chronic wounds. However, this shift was not confirmed in the wound tissues. Instead, the chronic wound tissues showed increased levels of MMP9, a known activator of TGF-ß. However, regulation of TGF-ß target genes, such as CTGF, COL1A1, or IL-6, was absent in the chronic wounds. In wound tissues, all three TGF-ß isoforms were expressed with increased levels of TGF-ß1 and TGF-ß3 and a reporter assay confirmed that the expressed TGF-ß was activated. However, Western blots and immunostaining showed decreased canonical TGF-ß signaling in the respective chronic wound tissues, suggesting the presence of a TGF-ß inhibitor. As a potential regulatory mechanism, the TGF-ß proteome profiler array suggested elevated levels of the TGF-ß pseudo-receptor BAMBI. Also, tissue expression of BAMBI was significantly increased not only in chronic wounds (10.6-fold) but also in acute wounds that had become chronic (9.5-fold). In summary, our data indicate a possible regulatory role of BAMBI in the development of chronic wounds. The available few in vivo studies support our findings by postulating a therapeutic potential of BAMBI for controlling scar formation.

Autologous Human Immunocompetent White Adipose Tissue-on-Chip.

Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In this era of "diabesity", white adipose tissue (WAT) has become a target of high interest for therapeutic strategies. To gain insights into mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models. Leveraging Organ-on-Chip technology, a microphysiological in vitro model of human WAT is introduced: a tailored microfluidic platform featuring vasculature-like perfusion that integrates 3D tissues comprising all major WAT-associated cellular components (mature adipocytes, organotypic endothelial barriers, stromovascular cells including adipose tissue macrophages) in an autologous manner and recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. A precisely controllable bottom-up approach enables the generation of a multitude of replicates per donor circumventing inter-donor variability issues and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity via a flexible mix-and-match approach. This WAT-on-Chip system constitutes the first human-based, autologous, and immunocompetent in vitro adipose tissue model that recapitulates almost full tissue heterogeneity and can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.

Immune-modulating properties of blue light do not influence reepithelization in vitro.

Phototherapy is gaining more attention in the treatment of various diseases. Especially, blue light seems to be a promising approach for wound healing promotion due to its antimicrobial and immune-modulating properties. Despite this, there is only little research focusing on the immune-modulating properties of blue light and its possible effects on wound healing. Therefore, we investigated the effects of blue light irradiation on peripheral blood mononuclear cells (PBMC) and the influence on reepithelization in vitro. PBMCs were irradiated with DermoDyne® (DermoDyne HealthCare, Berlin, Germany) and effects on cell viability, cytokine expression, and scratch wound closure were evaluated afterwards. Irradiated cells showed a higher Interleukin-γ concentration while irradiation reduced resazurin concentration in a time-dependent manner. No differences in reepithelization were detectable when keratinocytes were treated with the supernatant of these blue light irradiated PBMCs. Blue light-mediated ex vivo stimulation of PBMCs does not cause faster reepithelization in an in vitro setting. Further research is needed to investigate the wound healing effects of phototherapy with blue light.

Does Phototherapy Promote Wound Healing? Limitations of Blue Light Irradiation.

INTRODUCTION: Phototherapy is gaining increased attention in the research and treatment of various diseases. In particular, the use of blue light seems to bear promise, owing to its antimicrobial and immune-modulating properties; however, research focused on the effects of blue light on keratinocytes and reepithelization is rare. In addition, few studies to date have evaluated devices that are used in daily hospital routine. OBJECTIVE: This study investigated the effects of phototherapy on keratinocytes with 2 established devices in vitro. MATERIALS AND METHODS: Human adult low calcium high temperature keratinocytes were irradiated with 2 different devices, and the effects on scratch wound closure, proliferation, cell viability, and cytokine expression were evaluated. RESULTS: Blue light irradiation reduced reepithelization at high doses in a scratch wound healing model (wound closure on day 1: control group, 25.57 percentage points [PP] ± 2.36 standard deviation vs Device A for 10 minutes, 1.33 PP ± 1.01) and mitochondrial activity measured with resazurin conversion (Device A for 10 minutes, 33.28% ± 12.34). Irradiated cells demonstrated a lower ratio of proliferating cell nuclear antigen-positive cells and, as a result, lower proliferation. CONCLUSIONS: Blue light reduces keratinocyte proliferation and migration at high doses and therefore could negatively affect wound healing. Available irradiation devices for possible use in wound therapy should be critically scrutinized and evaluated with in vitro methods prior to clinical use.

Evaluation of a cross-linked versus non-cross-linked collagen matrix in full-thickness skin defects.

Autologous skin transplantation is the gold standard for treatment of full-thickness skin defects such as deep burn injuries, but has the disadvantages of limited donor sites and donor site morbidities. Alternative skin replacement products, such as xenografts and allografts, are not a permanent solution. Numerous manufactured skin substitutes already show promising approaches, but have limited efficacy. Therefore, wound dressings adaptable to the physiology of wound healing are still needed. In a randomized controlled in vivo study, a newly designed biocompatible collagen nonwoven matrix was compared to the Integra® bilayer dermal substitute and untreated controls in 48 full-thickness skin defects in a swine model. The take of all templates was complete, and all the tissue-engineered products accelerated dermal wound healing compared to the untreated controls, as identified by planimetric measurements. The higher collagen dose treatments and Integra®-covered wounds developed the thickest, cell-rich neoepidermal tissue in histological examination. The innovative biocompatible collagen matrix is flexibly applicable and modifiable, and offers potential as a carrier membrane for therapeutic supplemental products such as growth factors to further develop effective wound dressings.

Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery.

The finding that alterations in electrical potential play an important role in the mechanical stimulation of the bone provoked hype that noninvasive extremely low frequency pulsed electromagnetic fields (ELF-PEMF) can be used to support healing of bone and osteochondral defects. This resulted in the development of many ELF-PEMF devices for clinical use. Due to the resulting diversity of the ELF-PEMF characteristics regarding treatment regimen, and reported results, exposure to ELF-PEMFs is generally not among the guidelines to treat bone and osteochondral defects. Notwithstanding, here we show that there is strong evidence for ELF-PEMF treatment. We give a short, confined overview of in vitro studies investigating effects of ELF-PEMF treatment on bone cells, highlighting likely mechanisms. Subsequently, we summarize prospective and blinded studies, investigating the effect of ELF-PEMF treatment on acute bone fractures and bone fracture non-unions, osteotomies, spinal fusion, osteoporosis, and osteoarthritis. Although these studies favor the use of ELF-PEMF treatment, they likewise demonstrate the need for more defined and better controlled/monitored treatment modalities. However, to establish indication-oriented treatment regimen, profound knowledge of the underlying mechanisms in the sense of cellular pathways/events triggered is required, highlighting the need for more systematic studies to unravel optimal treatment conditions.